Social Decision Making in Parkinson's Disease

Cognitive and Neural Mechanisms of Impaired Social Decision-Making in Parkinson's Patients Taking Dopamine Agonists

Impulsive and compulsive behaviors occur in up to 46% of Parkinson's Disease (PD) patients taking dopamine agonist (DAA) medications. While these abnormal social behaviors have been studied in other neurodegenerative disorders, the true incidence of social problems, and the relationship to dopamine therapy, in PD patients remains unknown. This study is aiming to determine if dopamine agonists alter social decision-making and to determine if impaired social decision-making relates to dopamine-induced mesolimbic network dysfunction in PD patients. The protocol will include a screening visit, and on-DAA visit, and an off-DAA visit. For both the on and off DAA visits, participants will continue taking Carbidopa-Levodopa, but will withdrawal off of other PD related medications. Both visits will include an MRI, fMRI shock task, questionnaires to be filled out by other the participant and the caregiver, moral-decision making computer tasks, and the Unified Parkinsons Disease Rating Scale (UPDRS) part II and III. For the on-DAA visit, participants will take Pramipexole. For the off-DAA visit, participants will receive a placebo. Participants will remind blinded to which medication they are receiving that day and will be counterbalanced such that all participants will not take the Pramipexole or placebo on the same days.

Study Overview

• Status: Completed
• Conditions: Parkinson Disease
• Intervention / Treatment: Drug: Pramipexole; Drug: Placebo

Detailed Description

Impulsive and compulsive behaviors occur in up to 46% of Parkinson's Disease (PD) patients taking dopamine agonist (DAA) medications. While these abnormal social behaviors have been studied in other neurodegenerative disorders, the true incidence of social problems, and the relationship to dopamine therapy, in PD patients remains unknown. This study is aiming to determine if dopamine agonists alter social decision-making and to determine if impaired social decision-making relates to dopamine-induced mesolimbic network dysfunction in PD patients. The protocol will include a screening visit, and on-DAA visit, and an off-DAA visit. For both the on and off DAA visits, participants will continue taking Carbidopa-Levodopa, but will withdrawal off of other PD related medications to reduce circulating drugs and residual drug effects. Both visits will include an MRI, fMRI shock task, questionnaires to be filled out by other the participant and the caregiver, moral-decision making computer tasks, and the Unified Parkinson's Disease Rating Scale (UPDRS) part II and III. For the on-DAA visit, participants will take Carbidopa-Levodopa 1 hour before the scan and will take 1mg of Pramipexole 1 hour before the scan. For the off-DAA visit, participants will take Carbidopa-Levodopa 1 hour before the scan and will take a placebo 1 hour before the scan. Participants will remind blinded to which medication they are receiving that day and will be counterbalanced such that all participants will not take the Pramipexole or placebo on the same days.

• Study Type: Interventional
• Enrollment (Actual): 18
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Tennessee
    • Nashville, Tennessee, United States, 37212
      • Vanderbilt University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 45 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age 45-80
• Ability to give informed consent
• Idiopathic Parkinson's disease
• Currently taking dopamine agonist therapy
• Mild symptom severity (Hoehn & Yahr ≤ 3)
• Disease duration of <12 years
• Demonstrated positive response to dopamine therapy

Exclusion Criteria:

• Medications classes that influence GABA concentrations: benzodiazepines, cholinesterase inhibitors, antipsychotics, opioids, and MAO inhibitors
• History of substance abuse or use of any psychostimulants (other than caffeine) in the last 6 months or more than 4 times in lifetime
• Current tobacco (or nicotine use) or alcohol intake greater than 8 ounces of whiskey or equivalent per week
• Comorbid neurological disorders (e.g., stroke, peripheral neuropathy, seizure disorder) or history of head trauma (other than a single concussion)
• Unstable medical condition, [e.g., diabetes or pulmonary disease, significant medical condition, including high blood pressure (systolic B.P. > 135, Diastolic B.P. > 85), or any hepatic, renal, cardiovascular, hematological, endocrine or ophthalmological condition]
• History of major psychiatric illness (including any affective disorder, substance use disorder, psychotic disorder, or eating disorder)
• Dementia
• Deep brain stimulation
• Contraindications to 3 Tesla MRI, e.g., extreme obesity, claustrophobia, cochlear implant, metal fragments in eyes, cardiac pacemaker, neural stimulator, tattoos with iron pigment and metallic body inclusions or other metal implanted in the body
• Dyskinesia or tremor that would cause severe motion artifact during MRI scan
• Clear indication of secondary gain

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Impulsive group, placebo then pramipexole; half of the impulsive group will first get the placebo on the first day and pramipexole on the second day	Drug: Pramipexole; 1mg of pramipexole; Drug: Placebo; 1mg equivalent of placebo
Experimental: Impulsive group, pramipexole then placebo; half of the impulsive group will first get the pramipexole on the first day and the placebo on the second day	Drug: Pramipexole; 1mg of pramipexole; Drug: Placebo; 1mg equivalent of placebo
Experimental: Non-impulsive group, placebo then pramipexole; half of the non-impulsive group will first get the placebo on the first day and the pramipexole on the second day	Drug: Pramipexole; 1mg of pramipexole; Drug: Placebo; 1mg equivalent of placebo
Experimental: Non-impulsive, pramipexole then placebo; half of the non-impulsive group will first get the pramipexole on the first day and the placebo on the second day	Drug: Pramipexole; 1mg of pramipexole; Drug: Placebo; 1mg equivalent of placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The change in a harm aversion cognitive moral decision-making task	change in harm aversion from off drug visit to on drug visit	two weeks
change in blood flow in the ventral striatum per ASL images	change in CBF from off drug visit to on drug visit	two weeks

Collaborators and Investigators

• Sponsor: Vanderbilt University Medical Center
• Collaborators: United States Department of Defense
• Investigators: Principal Investigator: Richard R Darby, M.D., Vanderbilt University Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): December 3, 2019
• Primary Completion (Actual): June 1, 2022
• Study Completion (Actual): September 1, 2022

Study Registration Dates

• First Submitted: January 28, 2020
• First Submitted That Met QC Criteria: January 29, 2020
• First Posted (Actual): January 31, 2020

Study Record Updates

• Last Update Posted (Actual): October 18, 2023
• Last Update Submitted That Met QC Criteria: October 16, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: Impulsive behavior; dopamine agonists; Social decision making; Moral decision making
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Parkinsonian Disorders; Basal Ganglia Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Parkinson Disease; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Protective Agents; Dopamine Agonists; Dopamine Agents; Antioxidants; Antiparkinson Agents; Anti-Dyskinesia Agents; Pramipexole
• Other Study ID Numbers: Social Decision Making in PD; W81XWH-19-1-0782 (Other Grant/Funding Number: Department of Defense)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No